# US 2019/0169618 A1 · Nucleic acids and methods for the treatment of pompe disease

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2019/0169618 A1
- Document ID: US20190169618A1
- Status: Published application
- Kind: A1
- Application number: 16/042,714
- Filed: 2018-07-23
- Published: 2019-06-06
- Earliest claimed: 2013-09-11
- Assignees: Synthena AG
- Applicants: Synthena AG
- Inventors: Luis GARCIA; Aurelie AVRIL
- Web page: https://patentgrep.com/patent/US20190169618A1

## CPC

- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- C12Y 302/0102: Alpha-glucosidase (3.2.1.20)
- C12N 2310/11: Antisense
- C12N 2310/315: Phosphorothioates
- C12N 2310/321: 2'-O-R Modification
- C12N 2320/33: Alteration of splicing
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES

## Abstract

The invention relates to nucleic acids and methods for restoring acid alpha-glucosidase (GAA) activity in patients with Pompe disease using splice-switching technology.

## Claims

### Claim 1

A nucleic acid molecule 10 to 50 nucleotides in length, complementary to a nucleotide sequence of the acid alpha-glucosidase pre-mRNA, said nucleic acid being able to correct the splicing of exon 2 of the acid alpha-glucosidase pre-mRNA.

### Claim 2 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleic acid molecule is able to correct the splicing of exon 2 of the human acid alpha-glucosidase pre-mRNA displaying the c.-32-13T>G mutation.

### Claim 3 (depends on 1)

The nucleic acid molecule according to claim 1, comprising a nucleotide sequence complementary to a sequence comprised in the region defined by positions [+3;+45] of exon 2 of the GAA gene.

### Claim 4 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleotide sequence is complementary to one or more of the sequences defined by positions 3-17, 7-21 or 17-31 in SEQ ID NO:1 or in a sequence having at least 90% homology with SEQ ID NO:1.

### Claim 5 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleotide sequence is complementary to one of the sequences comprising SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:12 and SEQ ID NO:13.

### Claim 6 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleic acid molecule comprises a nucleotide sequence complementary to a sequence comprised in the region defined by positions [+3;+31] of exon 2 of the human GAA gene (SEQ ID NO:1).

### Claim 7 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleic acid molecule comprises or is an antisense oligonucleotide.

### Claim 8 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleic acid molecule comprises oligodeoxyribonucleotides, oligoribonucleotides, morpholinos, tricyclo-DNA-antisense oligonucleotides, tricyclo-phosphorothioate DNA-antisense oligonucleotides, LNA oligonucleotides and U7- or U1-modified nucleic acid molecule.

### Claim 9 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleic acid molecule comprises tricyclo-DNA-antisense oligonucleotides.

### Claim 10 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleic acid molecule comprises tricyclo-phosphorothioate DNA-antisense oligonucleotides.

### Claim 11 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleic acid molecule comprises a sequence selected from SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, and SEQ ID NO: 17.

### Claim 12 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleic acid molecule is linked to a modified U7 snRNA.

### Claim 13 (depends on 1)

A method for the treatment of Pompe disease, comprising administering the nucleic acid molecule of claim 1 to a patient in need thereof.

### Claim 14 (depends on 13)

The method according to claim 13, wherein the patient with Pompe disease harbors the c.-32 IVS1-13 T>G or an IVS1.-3 C>N mutation in the GAA gene.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising a nucleic acid molecule according to claim 1, in a pharmaceutically acceptable carrier.

### Claim 16 (depends on 6)

The nucleic acid molecule according to claim 6, wherein said sequence comprised in the region defined by positions [+3;+31] of exon 2 of the human GAA gene (SEQ ID NO:1) has a length from at least 10 to at most 29 nucleotides.

### Claim 17 (depends on 13)

The method according to claim 13, wherein the patient with Pompe disease harbors the c.-32-13 T>G mutation in the human GAA gene.

### Claim 18 (depends on 1)

The nucleic acid molecule according to claim 1, wherein all tc-nucleosides of said tricyclo-phosphorothioate DNA-antisense oligonucleotides are joined by inter nucleoside phosphorothioate linkages.

### Claim 19 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleic acid molecule comprises or consists of 2′-O-methyl-RNAs.

### Claim 20 (depends on 1)

The nucleic acid molecule according to claim 1, wherein said nucleic acid is a 2′-O-methyl-RNA with full phosphorothioate backbone.